Coagulation factor VII producing tumors and their release of microparticles with coagulation initiating capacity

• Project/Area Number: 21590455
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Single-year Grants
• Section: 一般
• Research Field: Experimental pathology
• Research Institution: 地方独立行政法人神奈川県立病院機構 (2011); Kanagawa Cancer Center Research Institute (2009-2010)
• Principal Investigator: MIYAGI Yohei 地方独立行政法人神奈川県立病院機構, 臨床研究所, 総括部長 (00254194)
• Co-Investigator(Kenkyū-buntansha): KOIZUME Shiro 神奈川県立がんセンター臨床研究所, 主任研究員 (60416063)
• Project Period (FY): 2009 – 2011
• Project Status: Completed (Fiscal Year 2011)
• Budget Amount: ¥4,550,000 (Direct Cost: ¥3,500,000、Indirect Cost: ¥1,050,000); Fiscal Year 2011: ¥1,040,000 (Direct Cost: ¥800,000、Indirect Cost: ¥240,000); Fiscal Year 2010: ¥1,820,000 (Direct Cost: ¥1,400,000、Indirect Cost: ¥420,000); Fiscal Year 2009: ¥1,690,000 (Direct Cost: ¥1,300,000、Indirect Cost: ¥390,000)
• Keywords: TF / 組織因子 / factor VII / 血液凝固第VII因子 / 低酸素 / 低血清 / 遺伝子発現 / 血液凝固 / 第VII / マイクロパーティクル / クルクミン / 低栄養

Research Abstract

Physiological expression of blood coagulation factor VII(fVII) is generally restricted to hepatocytes. In the present study, we found that breast cancer tumor cells produce fVII ectopically, and release fVII containing microparticles(MPs) with a high coagulation initiating capacity into the microenvironment, especially under hypoxic condition. In addition, we partly clarified a novel regulatory mechanism of gene expression under hypoxia combined with depleted nutrients, which could be a target for new cancer therapies.

Research Products

• [Journal Article] HIF2α-Sp1 interaction mediates a deacetylation-dependent FVII gene activation under hypoxic conditions in ovarian cancer cells (2012)
  • Author(s): Koizume S, Ito S, Miyagi E, Hirahara F, Nakamura Y, Sakuma Y, Osaka H, Takano Y, Ruf W, Miyagi Y.
  • Journal Title: Nucleic Acid Res Volume: 32(4) Pages: 1457-1461
• [Journal Article] HIF2α-Sp1 interaction mediates a deacetylation-dependent FVII-gene activation under hypoxic conditions in ovarian cancer cells (2012)
  • Author(s): Koizume S, Ito S, Miyagi E, Hirahara F, Nakamura Y, Sakuma Y, Osaka H, Takano Y, Ruf W, Miyagi Y
  • Journal Title: Nucleic Acid Research Volume: 40(12) Issue: 12 Pages: 5389-5401
  • DOI: 10.1093/nar/gks201
  • Peer Reviewed
• [Journal Article] Lung adenocarcinoma cells floating in lymphatic vessels resist anoikiswith Mcl-1 and E-cadherin expression. (2010)
  • Author(s): Sakuma Y, Takeuchi T, Nakamura Y, Yoshihara M, Matsukuma S, Nakayama H, Ohgane N, Yokose T, Kameda Y, Tsuchiya E, Miyagi Y.
  • Journal Title: Journal of Pathology Volume: 220(5) Pages: 574-585
  • Peer Reviewed
• [Journal Article] MDM2 gene amplification in colorectal cancer is associated with discaseprogression at the primary site, but inversely correlated with distant metastasis. (2010)
  • Author(s): Sugano N, Suda T, Godai T, Tsuchida K, Shiozawa M, Sekiguchi H, Yoshihara M, Matsukuma S, Sakuma Y, Tsuchiya E, Kameda Y, Akaike M, Miyagi Y.
  • Journal Title: Genes Chromosomes Cancer Volume: 49(7) Pages: 620-629
  • Peer Reviewed
• [Journal Article] Proteomic screening of completely resected tumors in relation to survival in patients with stage I non-small cell lung cancer (2010)
  • Author(s): Oshita F, Morita A, Ito H, Kameda Y, Tsuchiya E, Asai S, Miyagi Y.
  • Journal Title: Oncology Report Volume: 24 Pages: 637-645
  • Peer Reviewed
• [Journal Article] ETS family-associated gene fusions in Japanese prostate cancer: analysis of 194 radical prostatectomy samples. (2010)
  • Author(s): Miyagi Y, Sasaki T, Fujinami K, Sano J, Senga Y, Miura T, Kameda Y, Sakuma Y, Nakamura Y, Harada M, Tsuchiya E.
  • Journal Title: Modern Pathology Volume: 23(11) Pages: 1492-1498
  • Peer Reviewed
• [Journal Article] Secretion of intelectin-1 from malignant pleural mesothelioma into pleural effusion. (2010)
  • Author(s): Tsuji S, Tsuura Y, Morohoshi T, Shinohara T, Oshita F, Yamada K, Kameda Y, Ohtsu T, Nakamura Y, Miyagi Y.
  • Journal Title: British Journal of Cancer Volume: 103(4) Pages: 517-523
  • Peer Reviewed
• [Journal Article] Self-production of tissue factor-coagulation factor VII complex by ovarian cancer cells (2009)
  • Author(s): Yokota N, Koizume S, Miyagi E, Hirahara F, Nakamura Y, Kikuchi K, Ruf W, Sakuma Y, Tsuchiya E, Miyagi Y.
  • Journal Title: Br J Cancer Volume: 101 Pages: 2023-2029
• [Journal Article] HNF-4 independent synthesis of coagulation factor VII in breast cancer cells and its inhibition by targeting selective histone acetyltransferases (2009)
  • Author(s): Koizume S, Yokota N, Miyagi E, Hirahara F, Nakamura Y, Sakuma Y, Yoshida A, Kameda Y, Tsuchiya E, Ruf W, Miyagi Y.
  • Journal Title: Mol Cancer Res Volume: 7(12) Pages: 1928-1936
• [Journal Article] HNF-4 independent synthesis of coagulation factor VII in breast cancer cells and its inhibition by targeting selective histone acetyltransferases (2009)
  • Author(s): Koizume S, Yokota N, Miyagi E, Hirahara F, Nakamura Y, Sakuma Y, Yoshida A, Kameda Y, Tsuchiya E, Ruf W, Miyagi Y.
  • Journal Title: Molecular Cancer Research 7(12) Pages: 1928-1936
  • Peer Reviewed
• [Journal Article] Self-production of tissue factor-coagulation factor VII complex by ovarian cancer cells (2009)
  • Author(s): Yokota N, Koizume S, Miyagi E, Hirahara F, Nakamura Y, Kikuchi K, Ruf W, Sakuma Y, Tsuchiya E, Miyagi Y.
  • Journal Title: British Journal of Cancer 101 Pages: 2023-2029
  • Peer Reviewed
• [Presentation] 卵巣明細胞がん細胞においてHIF2α/Sp1/mTOR相互作用は脱アセチル化依存性転写を誘導する (2011)
  • Author(s): 小井詰史朗、宮城悦子、平原史樹、中村圭靖、高野康雄、宮城洋平
  • Organizer: 第70回日本癌学会学術総会
  • Place of Presentation: 名古屋
  • Year and Date: 2011-10-04
• [Presentation] (2011)
  • Author(s): Shiro Koizume, Etsuko Miyagi, Fumiki Hirahara, Yoshiyasu Nakamura, Eiju Tsuchiya, Wolfram Ruf, and Yohei Miyagi
  • Organizer: The 102nd AACR Annual Meeting 2011
  • Place of Presentation: Orlando, FL
  • Year and Date: 2011-10-03
• [Presentation] 卵巣明細胞がん細胞においてHIF2α/Sp1/mTOR相互作用は脱アセチル化依存性転写を誘導する (2011)
  • Author(s): 小井詰史朗、宮城悦子、平原史樹、中村圭靖、高野康雄、宮城洋平
  • Organizer: 第70回日本癌学会学術総会
  • Place of Presentation: 名古屋国際会議場、名古屋
  • Year and Date: 2011-10-03
• [Presentation] Hypoxic activation of FVII gene in cancer cells mediated by interaction among HIF2α, Sp1, and HDAC4 (2011)
  • Author(s): Shiro Koizume, Etsuko Miyagi, Fumiki Hirahara, Yoshiyasu Nakamura, Eiju Tsuchiya, Wolfram Ruf, Yohei Miyagi
  • Organizer: 第102回米国がん学会年会
  • Place of Presentation: オーランド,フロリダ
  • Year and Date: 2011-04-04
• [Presentation] MDM4遺伝子増幅大腸がんにおける臨床病理学的, 分子生物学的解析 (2010)
  • Author(s): 須田哲司, 吉原光代, 中村圭靖, 佐久間裕司, 亀田陽一, 赤池信, 土屋永寿, 松隈章一, 宮城洋平
  • Organizer: 第69回日本癌学会総会
  • Place of Presentation: 大阪
  • Year and Date: 2010-09-24
• [Presentation] 血漿遊離アミノ酸プロファイルに基づく新規マーカー, アミノインデックスによる前立腺がんのスクリーニング (2010)
  • Author(s): 三浦猛, 森山正敏, 池田伊知郎, 猿木信裕, 山本浩史, 今泉明, 光島徹, 山門實, 宮城洋平
  • Organizer: 第69回日本癌学会総会
  • Place of Presentation: 大阪
  • Year and Date: 2010-09-24
• [Presentation] KRAS遺伝子のコドン12, 13における変異の簡易迅速診断法-ループ・ハイブリッドLH変法- (2010)
  • Author(s): 松隈章一, 吉原光代, 宮城洋平
  • Organizer: 第69回日本癌学会総会
  • Place of Presentation: 大阪
  • Year and Date: 2010-09-24
• [Presentation] Activation of FVII gene in ovarian cancer cells associated with HIF2alpha-Sp1 interaction and histone deacetylation (2010)
  • Author(s): Shiro Koizume, Etsuko Miyagi, Fumiki Hirahara, Yoshiyasu Nakamura, Eiju Tsuchiya, Yohei Miyagi
  • Organizer: 第69回日本癌学会学術総会
  • Place of Presentation: リーガロイヤルホテル,大阪
  • Year and Date: 2010-09-23
• [Presentation] 卵巣がん細胞におけるFVII遺伝子発現誘導にはHIF2α-Sp 1相互作用とピストン脱アセチル化が関与する (2010)
  • Author(s): 小井詰史朗, 宮城悦子, 平原史樹, 中村圭靖, 土屋永寿, 宮城洋平
  • Organizer: 第69回日本癌学会総会
  • Place of Presentation: 大阪
  • Year and Date: 2010-09-23
• [Presentation] Src阻害薬とBcl-2阻害 ABT-263の併用療法は肺腺癌細胞のanoikis抵抗性を克服する (2010)
  • Author(s): 佐久間裕司, 中村圭靖, 吉原光代, 小井詰史朗, 宮城洋平
  • Organizer: 第69回日本癌学会総会
  • Place of Presentation: 大阪
  • Year and Date: 2010-09-22
• [Presentation] 血漿遊離アミノ酸プロファイルに基づく新規マーカー"アミノインデックス"によるがんのスクリーニング (2010)
  • Author(s): 宮城洋平, 東山聖彦, 合地明, 三浦猛, 猿木信裕, 石川孝, 赤池信, 今泉明, 山本浩史, 安東敏彦, 山門實, 岡本直幸
  • Organizer: 第69回日本癌学会総会
  • Place of Presentation: 大阪
  • Year and Date: 2010-09-22
• [Presentation] Probability of plasma amino acid concentration and its profileas a novel diagnostic marker for prostate cancer. (2010)
  • Author(s): Miyagi Y, Miura T, Moriyama M, Ohta J, Muramatsu T, Imaizumi A, Yamamoto H, Yamakado M, Okamoto N.
  • Organizer: The 101^<th>. AACR Annual Meeting 2010
  • Place of Presentation: Washington, DC
  • Year and Date: 2010-04-20
• [Presentation] Hypoxic induction of coagulation factor VII(FVII) in ovarian cancer cells associated with activation of blood coagulation (2009)
  • Author(s): Shiro Koizume and Yohei Miyagi
  • Organizer: The 7^<th> annual Meeting for the Japanese Association for Cancer and Hypoxia Research.第7回がんとハイポキシア研究会
  • Place of Presentation: 京都
  • Year and Date: 2009-12-05
• [Presentation] Curcumin Inhibits Ectopic Human Coagulation Factor VII Synthesis in Breast Cancer Cells by Targeting p300/CBP Activity (2009)
  • Author(s): Shiro Koizume, Naho Yokota, Etsuko Miyagi, Fumiki Hirahara, Yoshiyasu Nakamura, Akira Yoshida, Eiju Tsuchiya, Wolfram Ruf, and Yohei Miyagi
  • Organizer: 第68回日本癌学会学術総会
  • Place of Presentation: 横浜
  • Year and Date: 2009-10-03
• [Presentation] Release of TF/fVIIa Positive Highly-coagulating Microparticles from Ovarian Cancer Cellsand Its Increse Under Hypoxia (2009)
  • Author(s): Naho Yokota, Shiro Koizume, Yoshiyasu Nakamura, Yuji Sakuma, Mikiko-Asai Sato, Etsuko Miyagi, Fumiki Hirahara, Eiju Tsuchiya, Yohei Miyagi
  • Organizer: 第68回日本癌学会学術総会
  • Place of Presentation: 横浜
  • Year and Date: 2009-10-01
• [Presentation] Curcumin inhibits ectopic human coagulation factor VII synthesis in breast cancer cells by targeting p300/CBP activity (2009)
  • Author(s): Shiro Koizume, Naho Yokota, Etsuko Miyagi, Fumiki Hirahara, Yoshiyasu Nakamura, Akira Yoshida, Eiju Tsuchiya, Wolfram Ruf, Yohei Miyagi
  • Organizer: 第68回日本癌学会総会
  • Place of Presentation: 横浜
  • Year and Date: 2009-10-01
• [Presentation] Release of TF/fVIIa positive highly-coagulating microparticles from ovarian cancer cells and its increse under hypoxia (2009)
  • Author(s): Yokota N, Koizume S, Miyagi E, Hirahara F, Nakamura Y, Yoshida A, Tsuchiya E, Ruf W, Miyagi Y
  • Organizer: 第68回日本癌学会総会
  • Place of Presentation: 横浜
  • Year and Date: 2009-10-01
• [Presentation] Curcumin inhibits ectopic human coagulation factor VII synthesis in breast cancer cells by targeting p300/CBP activity (2009)
  • Author(s): Shiro Koizume, Naho Yokota, Etsuko Miyagi, Fumiki Hirahara, Yoshiyasu Nakamura, Akira Yoshida, Eiju Tsuchiya, Wolfram Ruf, Yohei Miyagi
  • Organizer: 米国がん学会年会(AACR2009)
  • Place of Presentation: コロラド州デンバー
  • Year and Date: 2009-04-21
• [Book] Functional Correlates, and Potential for a New Therapeutic Target. Breast Cancer. Current and Alternative Therapeutic Modalities (2011)
  • Author(s): Shiro Koizume and Yohei Miyagi
  • Publisher: InTech